PROJECT SUMMARY Background: Electronic cigarettes (e-cigarettes) are battery-operated devices that generate an aerosol (called ?vapor?) that is inhaled by the user. Despite their increasing popularity and use worldwide, little is known about their health effects. There is concern that e-cigarettes could expose users to metals, since a metal coil is used to generate the ?vapor?, and most coils are composed of nickel and chromium, which are known inhalation carcinogens. Our goal is to evaluate how e-cigarette use patterns impact exposure to toxic metals. Specific Aims: 1) to understand the role of metal heating components on the transfer of metals into the aerosol, by analyzing metal concentrations in e-liquid before it is in contact with the heating coil, in the aerosol generated, and in e-liquid after it has been in contact with heating coil, 2) Using a questionnaire, we will characterize patterns of e-cigarette use and other potential sources of metal exposures, and 3) we will measure metals in blood, urine, saliva, and exhaled breath condensate (EBC) of users, non users, smokers and dual users, to evaluate how different patterns of e-cigarette and smoking use impact metal exposure. Preliminary studies: We have found nickel, chromium, and lead in aerosol from e-cigarettes, and also in urine, saliva and EBC of current e-cigarette users. All metal levels measured in the aerosol and in the e-liquid after being heated were higher than the metal levels found in e-liquid that was not in contact with the coil. We also found that use behaviors, such as frequency of use and e-cigarette voltage, were associated with exposure levels. Design and setting: We will recruit men and women of all racial and ethnic backgrounds that will be assigned to one of four categories: 1) e-cigarette users, 2) cigarette smokers, 3) dual users (use both e-cigarettes and combustible tobacco products), and 4) non-users/smokers. Data collection: All participants will answer a questionnaire on smoking history, e-cigarette use patterns, and work/hobbies that may involve metal use. Samples of blood, urine, saliva, and exhaled breath will be collected to measure and compare metal levels within and between groups. For e-cigarette users, samples of their e-liquid before use, after heating with the coil, and vapor generated will also be collected to understand the transfer of metals during e-cigarette use. Statistical Analysis: Linear regression models will be used to estimate the association of metals in biomarkers with e-cigarette use patterns, cotinine biomarkers, and metal concentrations in e-liquid and aerosol. For urine biomarkers, all models will be adjusted for urinary creatinine. Significance: The proposed project will allow us to evaluate e-cigarette users? exposure to metals, how their use patterns impact their metal exposures, and how their metal exposure levels compare to that of cigarette smokers, dual users, and non-users/smokers. This study will generate information needed to inform policy-level interventions for e-cigarette regulation as well as to plan future studies on the health effects of e-cigarette use.